An investigation of a novel redox-mediated regulation of protein kinase G in the heart

心脏中蛋白激酶 G 的新型氧化还原介导调节的研究

• 批准号: G0700320/1
• 负责人: Philip Eaton
• 金额: $ 84.72万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0700320%2F1
• 关键词: investigation; novel; redox; mediated; regulation

Free radicals and oxidising chemicals are produced in cells and tissues. Historically these have been primarily associated with disease or dysfunction. However, over the past decade there has been a growing realisation that these species are not always harmful, and in fact they can play important regulatory roles. We have found in preliminary studies that a protein (known as protein kinase G, specifically the 1 alpha isoform), which is very important for how the heart is regulated is chemically modified by oxidants and this directly activates it. Here we outline studies that will help fully define the importance of this modification and activation of protein kinase G, both in health and in disease. We will utilise many experimental approaches in this work, including generation of a genetically modified mouse that has been altered so that it cannot be oxidised and directly activated by oxidants. The availability of such mice would be an invaluable resource that will allow us to study fully the importance of oxidant-induced protein kinase A activation in cells, tissues, organs and the animal as a whole.

细胞和组织中产生自由基和氧化化学物质。从历史上看，这些主要与疾病或功能障碍有关。然而，在过去的十年中，人们越来越认识到这些物种并不总是有害的，事实上它们可以发挥重要的调节作用。我们在初步研究中发现，一种对于心脏调节非常重要的蛋白质（称为蛋白激酶 G，特别是 1 α 同工型）会被氧化剂进行化学修饰，从而直接激活它。在这里，我们概述了一些研究，这些研究将有助于充分确定蛋白激酶 G 的这种修饰和激活对于健康和疾病的重要性。我们将在这项工作中利用许多实验方法，包括生成经过改造的转基因小鼠，使其不能被氧化剂氧化和直接激活。此类小鼠的可用性将是一种宝贵的资源，使我们能够充分研究氧化剂诱导的蛋白激酶 A 激活在细胞、组织、器官和整个动物中的重要性。